The overall objective of this project is to develop a general and completely integrated system of computer programs for the determination of macromolecular structures by X-ray crystallography. A new technique is proposed for obtaining accurate atomic coordinates for macromolecules. This technique is based on a least-squares treatment of atomic shift vectors obtained from difference electron density syntheses. It should provide a convenient and economical method of obtaining accurate structural information for studies of enzymatic catalysis, allostery, protein folding, and evolutionary homologies. Generalized routines will be included in the computing system for all routine crystallographic calculations, as well as for newer techniques of solving or refining macromolecular structures, such as the molecular replacement method. A minicomputer will be incorporated as an integral component of the system for the performance of those tasks, such as acquisition and initial processing of raw data, for which it is best suited. A large batch-processing computer will be used for the remaining tasks. Use of a higher-level language will permit easy modification of the system for use in other laboratories. Thorough testing and detailed documentation of the system will be carried out as essential steps in assuring its effective utilization. Where appropriate, testing will be carried out with actual experimental data. The system will be developed as a kind of research resource and made freely available to all interested crystallographers. BIBLIOGRAPHIC REFERENCES: Becker, J.W., Reeke, G.N. Jr., Cunningham, B.A., and Edelman, G.M. New evidence on the location of the saccharide-binding site of concanavalin A. Nature 259, 406-409 (1976).